2025/10/03 by Martin Grønbæk-Thygesen, Caroline Kampmeyer, Paula Eschger +6 · 1 voice · 1 citation
Biochemistry, Genetics and Molecular Biology · #Amyotrophic lateral sclerosis #Autophagy #Domain (mathematical analysis) #Glycosylation and Glycoproteins Research #Protein Tyrosine Phosphatases #Protein degradation #Protein domain #Ubiquitin #Ubiquitin and proteasome pathways
paper · pdf · doi:10.1101/2025.10.02.679934
published in bioRxiv (Cold Spring Harbor Laboratory) (Cold Spring Harbor Laboratory)
openalex publication_date 2025/10/03 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Abstract UBQLN2 is a member of the UBL-UBA domain protein family that functions as extrinsic substrate receptors for the 26S proteasome. UBQLN2 has been shown to undergo phase separation in vitro . In cells, UBQLN2 forms condensates that may be of importance for tuning protein degradation via the ubiquitin-proteasome system and potentially of relevance for UBQLN2 -linked amyotrophic lateral sclerosis (ALS). Here we show that UBQLN2 is ubiquitylated on lysine residues in the N-terminal UBL domain. The C-terminal region of UBQLN2 is lysine-depleted, and we show that introducing lysine residues in this region leads to its E6AP-dependent degradation. The UBL domain critically stabilizes UBQLN2 and protects it from proteasomal degradation. Fusion of ubiquitin to the UBQLN2 N-terminus stabilizes UBQLN2 and increases its propensity for locating in puncta, indicating that ubiquitylation of the UBQLN2 UBL domain regulates abundance and localization.